Neuromyelitis optica spectrum disorder (NMOSD) is a rare and chronic autoimmune disorder of the central nervous system (CNS) that typically presents with inflammation to the optic nerves (optic neuritis) and the spinal cord (acute transverse myelitis).1,2 Three agents were recently approved for NMOSD treatment in adults, leading to a renewed focus on this disorder.

The disorder was regarded as a subtype of multiple sclerosis (MS) but later was found to have clinical, laboratory, and neuroimaging characteristics that are distinct from MS (Table 1).1,4-14 Many cases of NMOSD (>20%) are still misdiagnosed as MS.7

Table 1. Characteristics of NMOSD vs Multiple Sclerosis

CharacteristicNMOSD4-10Multiple Sclerosis5,6,11-14
 1-3 per 100,000 persons worldwide3.6 cases per 100,000 persons in women and 2.0 in men
 Greater frequency in individuals of Asian or African descent and non-EuropeansCommon in northern and southern hemispheres, distant from the equator; people with northern European ancestry are at a greater risk
Age of onset32-41 years of age (median age, 39 years) but cases have been identified in children and older adultsMedian age, 29 years, uncommon in children and adults >50 years of age
F:M2:1 (children) to 10:1 (adults) with high female predominanceFemale predominance; 3 times more likely in women than men
 Antibody immune response against AQP4 water channels or MOG lead to astrocytic damage, demyelination, and inflammation in CNS

Other environmental factors may also lead to onset
Mainly T-cell driven autoimmune response against proteins of myelin sheath (ie, myelin basic protein) MOG is a major antigen that can be directing the B cell response as well

Genetic and other environmental factors may also lead to onset
Common signs and symptoms  
 Optic neuritis (25%), severe myelitis on first attack with paraplegia (30%-70%), and APS (intractable hiccup and nausea; 16%-44%)Weakness or diminished dexterity in ≥1 limbs, a sensory disturbance, optic neuritis, diplopia, gait instability, and ataxia

Bladder dysfunction, fatigue, and heat sensitivity can occur in patients as disease progresses
MRI findings  
Spinal cordMore severe atrophy of spinal cord

Longitudinal, continuous lesions extend over ≥3 contiguous vertebral segments associated with acute myelitis (94% adults and 100% pediatrics)

FLAIR hyperintense spotty bright lesions on T2WI (54%)

T1-weighted gadolinium-enhancing lesion extending over optic chiasm or optic nerve

Lesions specifically form in areas of high AQP4-Ab expression: peri-ependymal white matter around the third ventricle, hypothalamus, periaqueductal grey matter and dorsal aspect of the brainstem adjacent to the fourth ventricle and signal abnormalities in the area postrema
Lesions are usually about 1 vertebral segment long or less

FLAIR hyperintense ovoid plaques on T2WI

Plaques may demonstrate enhancement on post gadolinium T1WI

Plaques are hypointense on unenhanced T1WI (80%) and can demonstrate “black holes” of axonal loss and merge in advanced stages

BrainLesions located generally near ventricles, in the diencephalon and hypothalamusMore severe atrophy of the brain

Lesions adjacent to lateral ventricles and temporal lobe, Dawson finger type lesions perpendicular to lateral ventricles
Optic nerveBilateral optic neuritis extending to optic chiasmOptic neuritis does not typically extend to optic chiasm
Cerebrospinal fluid  
OCBPresent in patients (33%-43%) and disappear in follow-up samplingOCB present in
most patients (97%)
PleocytosisSevereMild to moderate
Polyspecific antiviral humoral immune response (eg, against MRZ)Rare (5%)Common (88%)
 Disease progression can be faster

Poor depending if frequent attacks during the first 2 years of the disease, first attack is severe, or coexistence of SLE and/or other autoimmune disorders

Survival rate of 90% (monophasic)and 68% (relapsing)  
Disease progression can be slower

Poor depending if ≥40 years of age at disease onset, location of lesions formation, male, non-White, initial motor deficits, frequent attacks during the first few years of the disease
APS, area postrema syndrome; FLAIR, fluid-attenuated inversion recovery; MRI, magnetic resonance imaging; OCB, oligoclonal bands; SLE, systemic lupus erythematosus; T1WI, T1-weighted image; T2WI, T2-weighted image

Although NMOSD is typically a sporadic disease, approximately 3% of cases occur in patients with a family history of NMOSD.2,4  This disease occurs in people of all races at a rate of 1 to 3 per 100,000 persons worldwide; however, NMOSD is more common than MS in Asian and Black populations.4 Specifically, the prevalence of NMOSD is lowest (1%-2%) in White populations from North America or Australia, and highest (20%-48%) in people from the West Indies and Asia.4 Additionally, the mortality rate from NMOSD is higher in Black patients compared with other races and ethnicities.14

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Although the median age of onset is 39 years, individuals of any age may be affected.2,4,14 NMOSD is found more often in women than in men with ratios ranging from 2:1 to 10:1, according to worldwide reports.4 Study findings also suggest that there may be exogenous risk factors that lead to the onset of NMOSD, such as low vitamin D exposure and infections, but further research is being conducted to confirm these correlations.7,12,13